System and method incorporating solid buffer

ABSTRACT

A buffered suspension includes a surfactant and a solid buffer particulate having a point of zero charge at least 1.2 pH units different that the pH of the buffered suspension. The buffered suspension can be prepared by mixing a stock solution with the solid buffer particulate and titrating. A method of preforming a pH sensitive process includes drawing the buffered suspension from a reservoir, filtering the solid buffer particulate from the buffered suspension, and applying the filtered solution to a sensor.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims benefit of U.S. Provisional Application No.62/014,636, filed Jun. 19, 2014, which is incorporated herein byreference in its entirety.

This application claims benefit of U.S. Provisional Application No.62/036,303, filed Aug. 12, 2014, which is incorporated herein byreference in its entirety.

FIELD OF THE DISCLOSURE

This disclosure, in general, relates to systems and methodsincorporating a solid buffer in reagent solutions.

BACKGROUND

As research and medical testing seeks to characterize smallconcentrations of complex molecules, the sensitivity of instruments isincreasingly susceptible to changes in pH. Further, such advancedsensing and testing methods rely on expensive reagents that aredifficult to prepare. In a particular example, sequencing of nucleicacids or proteins relies on specialized solutions, such as nucleotidesolutions that include expensive components. Such testing methodsutilizing such specialized solutions can be pH sensitive.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure may be better understood, and its numerousfeatures and advantages made apparent to those skilled in the art byreferencing the accompanying drawings.

FIG. 1 includes a flow diagram illustrating an exemplary method forutilizing a buffered suspension.

FIG. 2 includes a flow diagram illustrating an exemplary method forformulating a buffered suspension.

FIG. 3 includes an illustration of an exemplary testing apparatus usinga buffered suspension.

FIG. 4 includes a graph illustrating the response of a bufferedsuspension to a strong acid.

The use of the same reference symbols in different drawings indicatessimilar or identical items.

DETAILED DESCRIPTION

In an exemplary embodiment, a buffered suspension includes a surfactantand a solid buffer particulate. The buffered suspension has a target pH.The solid buffer particulate may be a ceramic buffer particulate thathas, for example, a point of zero charge that is at least 1.2 pH unitsdifferent than the target pH of the suspension. In use, the suspensioncan be drawn from a reservoir and the solid buffer particulate filteredfrom the suspension. The filtered solution can be applied over a sensoror can be used to form other reagent solutions from reagentconcentrates. In an example, the buffered suspension can be formulatedby mixing a stock solution including the surfactant and optionally othercomponents with the solid buffer particulate to form a suspension. Thesuspension can be titrated either with an acid or base to a target pH.The solid buffer particulate can be allowed to settle and a portion ofthe stock solution can be decanted. Additional stock solution can beadded and the process repeated. Subsequently, the suspension can beplaced in bottles for transportation or cartridges for insertion intothe sensor system.

In particular, the buffered suspension can include a surfactant and asolid buffer particulate. The buffer suspension has pH within a targetrange. For example, the target pH can be within a range of 6.0 to 8.0,such as a range of 6.8 to 8.0, a range of 7.2 to 8.0, or even a range of7.4 to 8.0. Alternatively, the target pH can be in a range of 5.0 to6.0. In a further alternative, the target pH can be in a range of 9.0 to11.0.

The solid buffer particulate can include a ceramic particulate. In anexample, the ceramic particulate can be titanium dioxide, tin oxide,zirconia, alumina, tantalum oxide, or a combination thereof. Forexample, the ceramic particulate can be a titanium dioxide or tin oxide.In a particular example, the ceramic particulate includes titaniumdioxide. Further, the ceramic particulate can be a hydrolyzed ceramicparticulate or can be a fumed ceramic particulate. In particular, theceramic particulate is a fumed ceramic particulate.

The solid buffer particulate, such as a ceramic particulate, can have apoint of zero charge at least 1.2 pH units different than the target pH.For example, the point of zero charge can be at least 2.0 pH unitsdifferent than a target pH or at least 3.0 pH units different than thetarget pH, but not greater than 10 pH units different than the targetpH. In particular, the solid buffer particulate has a point of zerocharge that is less than the target pH of the suspension. Alternatively,the solid buffer particulate can have a point of zero charge that isgreater than the target pH of the suspension. In a further alternative,a combination of solid buffer particulates can be used. For example, acombination including a solid buffer particulate having a point of zerocharge below the target pH and a solid buffer particulate having a pointof zero charge above the target pH can be used.

Further, the solid buffer particulate can have a specific surface areain the range of 10 m²/g to 350 m²/g. For example, the specific surfacearea can be in a range of 50 m²/g to 350 m²/g, such as a range of 100m²/g to 300 m²/g, a range of 150 m²/g to 300 m²/g, or even a range of225 m²/g to 275 m²/g. In another example, the specific surface area canbe in a range of 25 m²/g to 125 m²/g, such as a range of 50 m²/g to 100m²/g. Further, the solid buffer particulate can have a particle size,such as an average agglomerate size, in a range of 0.01 μm to 1200 μm.For example, the average particle size can be in a range of 0.05 μm to500 μm, such as a range of 0.5 μm to 200 μm, or even a range of 5.0 μmto 100 μm.

The suspension can include the solid buffer particulate in a range of 1g/L to 100 g/L, such as a range of 5 g/L to 75 g/L, a range of 10 g/L to65 g/L, a range of 20 g/L to 50 g/L, or even a range of 25 g/L to 40g/L.

The suspension can include one or more surfactants having a totalconcentration in the range of 0.001% to 1.0% by weight. For example, thesurfactant can be included in an amount in a range of 0.005% to 0.8%,such as a range of 0.005% to 0.5% by weight.

The surfactant can be an ionic surfactant, an amphoteric surfactant, anon-ionic surfactant, or a combination thereof. Optionally, thesurfactant can include a zwitterion. The ionic surfactant can be ananionic surfactant. An exemplary anionic surfactant includes a sulfatesurfactant, a sulfonate surfactant, a phosphate surfactant, acarboxylate surfactant, or any combination thereof. An exemplary sulfatesurfactant includes alkyl sulfates, such as ammonium lauryl sulfate,sodium lauryl sulfate (sodium dodecyl sulfate, (SDS)), or a combinationthereof; an alkyl ether sulfate, such as sodium laureth sulfate, sodiummyreth sulfate, or any combination thereof; or any combination thereof.An exemplary sulfonate surfactant includes an alkyl sulfonate, such assodium dodecyl sulfonate; docusates such as dioctyl sodiumsulfosuccinate; alkyl benzyl sulfonate (e.g., dodecyl benzene sulfonicacid or salts thereof); or any combination thereof. An exemplaryphosphate surfactant includes alkyl aryl ether phosphate, alkyl etherphosphate, or any combination thereof. An exemplary carboxylic acidsurfactant includes alkyl carboxylates, such as fatty acid salts orsodium stearate; sodium lauroyl sarcosinate; a bile acid salt, such assodium deoxycholate; or any combination thereof.

In another example, the ionic surfactant can be a cationic surfactant.An exemplary cationic surfactant includes primary, secondary or tertiaryamines, quaternary ammonium surfactants, or any combination thereof. Anexemplary quaternary ammonium surfactant includes alkyltrimethylammoniumsalts, such as cetyl trimethylammonium bromide (CTAB) or cetyltrimethylammonium chloride (CTAC); cetylpyridinium chloride (CPC);polyethoxylated tallow amine (POEA); benzalkonium chloride (BAC);benzethonium chloride (BZT); 5-bromo-5-nitro-1,3-dioxane;dimethyldioctadecylammonium chloride; dioctadecyldimethylammoniumbromide (DODAB); or any combination thereof.

An exemplary amphoteric surfactant includes a primary, secondary, ortertiary amine or a quaternary ammonium cation and a sulfonate,carboxylate, or phosphate anion. An exemplary sulfonate amphotericsurfactant includes(3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate); a sultainesuch as cocamidopropyl hydroxysultaine; or any combination thereof. Anexemplary carboxylic acid amphoteric surfactant includes amino acids,imino acids, betaines such as cocamidopropyl betaine, or any combinationthereof. An exemplary phosphate amphoteric surfactant includes lecithin.In a further example, the surfactant can be a sulfobetaine surfactant oran amidosulfobetaine.

In another example, the surfactant can be a non-ionic surfactant such asa polyethylene glycol-based surfactant, an alkyl pyrrolidine surfactant,an alkyl imidazolidinone surfactant, an alkyl morpholine surfactant, analkyl imidazole surfactant, an alkyl imidazoline surfactant, or acombination thereof. In a particular example, thepolyethylene-glycol-based surfactant includes a polyethylene-glycolether, such as an alkylphenol polyethoxylate, such as octyl phenolethoxylate or a polyoxyethylene alkyl phenyl ether, or a combinationthereof. In another example, the non-ionic surfactant includes anon-ionic fluorosurfactant, such as an ethoxylated fluorocarbon. In afurther example, the suspension can include octyl pyrrolidine.

Further, the suspension can include a biocide. In a particular example,the biocide can be an isothiazolinone biocide. For example, the biocidecan be 2-methyl4-isothiazoline-3-one.

The suspension can include salts, such as magnesium salt, potassiumsalt, sodium salt, or a combination thereof. For example, the suspensioncan include potassium salt, such as potassium chloride, in a range of 5mM to 150 mM, such as a range of 10 mM to 100 mM or a range of 40 mM to70 mM. In another example, the suspension can include a magnesium salt,such as magnesium chloride or magnesium sulfate, in a range of 1 mM to100 mM, such as a range of 5 mM to 75 mM or a range of 5 mM to 30 mM. Ina further example, the suspension can include sodium salt, such assodium chloride, in a range of 5 mM to 150 mM, such as a range of 10 mMto 100 mM or a range of 40 mM to 70 mM.

As illustrated in FIG. 1, a method 100 includes drawing a suspensionfrom a reservoir, as illustrated at 102. The suspension includes a solidbuffer particulate and can include a surfactant. The suspension isfiltered, as illustrated at 104, to remove the solid buffer particulateand form a filtered solution. The filter solution can be used to mixwith a reagent concentrate to form a reagent solution, as illustrated at106. The reagent solution or the filtered solution can flow over asensor, as illustrated at 108, as part of a process for testing,measuring or sensing. In a particular example, alternate flows of thefiltered solution and reagent solutions can flow over the sensor. Assuch, the filtered solution can act as a wash solution between flows ofthe reagent solutions. The sensor can be a pH sensor. In a particularexample, the sensor may be a biosensor, such as a semiconductorsequencing device. An exemplary semiconductor sequencing device can relyon pH to perform sequencing-by-synthesis.

The suspension can include a stock solution and a solid bufferparticulate. As illustrated in FIG. 2, a method 200 includes mixing astock solution with a solid buffer particulate to form a suspension, asillustrated at 202. The stock solution can include the components of thefinal buffered suspension, for example, as described above, absent thesolid buffer particulate. The dispersion is titrated to a target pH, asillustrated at 204. For example, the pH can be adjusted using a base oran acid. For example, the pH can be adjusted using a base, such assodium hydroxide, or an acid, such as hydrochloric acid.

As illustrated at 206, the solid buffer particulate can settle and aportion of the stock solution can be decanted, as illustrated at 208.The process can be repeated, mixing additional stock solution with thesolid buffer particulate, as illustrated at 202, titrating, asillustrated at 204, allowing the buffer particulate to settle, asillustrated at 206, and decanting a portion of the stock solution, asillustrated at 208. The process can be repeated once, twice, threetimes, or more. Subsequently, the solid buffer particulate can bere-dispersed within the suspension and applied to a cartridge useful ina system for sensing or testing, as illustrated at 210.

FIG. 3 includes an illustration of an exemplary system in which such abuffered suspension finds particular use. The exemplary bufferedsuspension finds particular use in biological processes where multiplereagents are delivered to one or more reactors or reaction sites. Thereaction sites may be monitored by chemical, electrical or opticalsensors. Exemplary systems include methods and apparatuses for carryingout DNA sequencing, and in particular, pH-based DNA sequencing. Forexample, in pH-based DNA sequencing, nucleotide base incorporations aredetermined by measuring hydrogen ions that are generated as naturalbyproducts of polymerase-catalyzed extension reactions. DNA templateseach having a primer and polymerase operably bound are loaded intoreaction chambers or microwells, after which repeated cycles ofdeoxynucleoside triphosphate (dNTP) addition and washing are carriedout. Such templates are typically attached as clonal populations to asolid support, such as a microparticle, bead, or the like, and suchclonal populations are loaded into reaction chambers. In each additionstep of the cycle, the polymerase extends the primer by incorporatingadded dNTP when the next base in the template is the complement of theadded dNTP. If there is one complementary base, there is oneincorporation, if two, there are two incorporations, if three, there arethree incorporations, and so on. With each such incorporation there is ahydrogen ion released, and collectively a population of templatesreleasing hydrogen ions causes very slight changes to the local pH ofthe reaction chamber which is detected by an electronic sensor. Inaddition to sequencing, the device herein may be useful for otherbiological instruments that require fluid storage or delivery.

FIG. 3 diagrammatically illustrates a system employing an enclosure 614that is a reagent reservoir, for example, for carrying out pH-basednucleic acid sequencing. Each electronic sensor of the apparatusgenerates an output signal. The fluid circuit permits multiple reagentsto be delivered to the reaction chambers.

In FIG. 3, the system includes a fluidics circuit 602 connected to thereagent reservoirs 614, to a waste reservoir 620, and to a biosensor 634by fluid pathway 632 that connects fluidics node 630 to inlet 638 ofbiosensor 634 for fluidic communication. The prepared and mixed reagentsolution from reservoirs 614 can be driven to fluidic circuit 602 by avariety of methods including pressure, pumps, such as syringe pumps,gravity feed, and the like, and are selected by control of valves 650.Reagents from the fluidics circuit 602 can be driven to the wastecontainers 620 and 636. The control system 618 includes controllers forvalves 650 that generate signals for opening and closing via anelectrical connection 616.

The control system 618 also includes controllers for other components ofthe system, such as a wash solution valve 624 connected thereto by theelectrical connection 622, and the reference electrode 628. The controlsystem 618 can also include control and data acquisition functions forthe biosensor 634. In one mode of operation, the fluidic circuit 602delivers a sequence of selected reagents 1, 2, 3, 4, or 5 to thebiosensor 634 under programmed control of the control system 618, suchthat in between selected reagent flows, the fluidics circuit 602 isprimed and washed with a wash solution 626, and the biosensor 634 iswashed with the wash solution 626. Fluids entering the biosensor 634exit through the outlet 640 and are deposited in the waste container636. A similar setup may be used for optical sequencing systems, withphotodiodes or CCD cameras, for example.

In a particular example, the wash solution 626 can be a bufferedsuspension including the solid buffer particulate. The buffer suspension(wash solution) can be filtered using a filter 660 before entering thefluidics circuit 602 or sensor 634. In a further example, the bufferedsuspension can be applied to the reagent reservoirs 614 through filter662 to form the reagent solutions from reagent concentrate within thereagent reservoirs. Alternatively, the filter 660 and 662 can be thesame filter. In an example, the reagent concentrate is a liquidconcentrate. In another example, the reagent concentrate is a driedconcentrate, such as a lyophilized reagent (e.g., lyophilizednucleotides). Alternatively, the illustrated filters 660 and 662 can becombined. In another example, filters can be located downstream of thereagent reservoirs 614, such as between the reagent reservoirs 614 andthe valves 650.

Aspects of the above methods, systems, and compositions providetechnical advantages, including a buffered suspension that counteractsacidification by outside influences, such as a carbon dioxide. Thesuspension can be filtered to remove buffering, allowing for use insystems that measure changes in pH. In particular, for systems using pHsensors, providing buffering during reagent transport or storage yetallowing for pH changes during use is problematic. Utilizing afilterable solid state buffer, allows robust pH control duringtransportation and storage, while presenting a solution useful insystems that utilize pH changes.

EXAMPLE Example 1

A suspension is prepared by the following procedure. Nitrogen purgeclean 2 liter bottles for 5 minutes, add 1880 ml 18 mOhm water, add 120ml wash solution, mix briefly under nitrogen.

The wash solution is prepared by the following process. Firstly, weigh200 g titanium oxide into clean 8 L carboy outfitted with spigot, add 8L PSP4 W2, keep carboy under nitrogen and mix with rotary mixer on standin chemistry area, add 20 ml M NaOH, mix for 30 minutes, check pH usingspecial glass pH probe with sliding sheath, keep probe suspended inslurry, titrate to pH 7.85 using 1M NaOH, adding 1 ml at a time, mix for10 minutes, stop mixing, allow slurry to settle for 30 minutes, andslowly decant top 4 L of liquid, limiting disturbance of titania.

Secondly, add freshly made 4 L PSP4 W2, mix 10 minutes, check pH andrecord, stop mixing, allow slurry to settle for 30 minutes, and slowlydecant top 4 L of liquid, limiting disturbance of titania, allow slurryto settle for 30 minutes, and slowly decant top 4 L of liquid, limitingdisturbance of titania.

Thirdly, add freshly made 4 L PSP4 W2, mix 10 minutes, check pH andrecord, stop mixing, allow slurry to settle for 30 minutes, slowlydecant down to 6 L volume of slurry, start mixing again, and bring pH to7.85 using 1M NaOH, adding ˜500 ul at a time.

Example 2

The pH response of a 100 mL sample including titania in a W2 solution ata concentration of 10 g/L is tested. An HCl solution is mixed with thesample and the pH response is measured. As illustrated in FIG. 4, the pHof the sample exhibits resistance to pH change in response to theaddition of the HCl.

In a first aspect, a method of performing pH-sensitive processesincludes drawing a suspension from a reservoir, the suspension includinga surfactant and a solid buffer particulate and having a target pH;filtering the solid buffer particulate from the suspension to form afiltered solution; and flowing the filtered solution over a sensor.

In a second aspect, a method of forming a suspension includes mixing astock solution and a solid buffer particulate to form a suspension, thestock solution comprising a surfactant; titrating the suspension to atarget pH; settling the solid buffer particulate from the suspension;and decanting a portion of the stock solution.

In a third aspect, a buffered suspension includes a surfactant and asolid buffer particulate having a point of zero charge at least 1.2 pHunits different that the pH of the buffered suspension.

In an example of the first, second, and third aspects, the solid bufferparticulate has a point of zero charge of at least 1.2 pH unitsdifferent than the target pH. For example, the point of zero charge isat least 2.0 pH units different than the target pH, such as at least 3.0pH units different than the target pH, but not greater than 10 pH unitsdifferent than the target pH.

In another example of the first, second, and third aspects and the aboveexamples, the target pH is in a range of 6 to 8. For example, the targetpH is in a range of 6.8 to 8.0, such as a range of 7.2 to 8.0 or a rangeof 7.4 to 8.0.

In a further example of the first, second, and third aspects and theabove examples, the solid buffer particulate includes a ceramicparticulate. For example, the ceramic particulate is titanium dioxide,tin oxide, zirconia, alumina, tantalum oxide, or a combination thereof.In an example, the ceramic particulate is titanium dioxide or tin oxide.In another example, the ceramic particulate is titanium dioxide. In aparticular example, the ceramic particulate is a fumed ceramicparticulate.

In an additional example of the first, second, and third aspects and theabove examples, the solid buffer particulate has a specific surface areain the range of 50 m²/g to 350 m²/g. For example, the specific surfacearea is in a range of 100 m²/g to 300 m²/g, such as a range of 150 m²/gto 300 m²/g, or a range of 225 m²/g to 275 m²/g. In an further exampleof the first, second, and third aspects and the above examples, thesolid buffer particulate has a specific surface area in the range of 25m²/g to 125 m²/g, such as in a range of 50 m²/g to 100 m²/g.

In another example of the first, second, and third aspects and the aboveexamples, the solid buffer particulate has a particle size in a range of0.01 microns to 1200 microns. For example, the particle size is in arange of 0.05 microns to 500 microns, such as a range of 0.5 microns to200 microns or a range of 5.0 microns to 100 microns.

In a further example of the first, second, and third aspects and theabove examples, the surfactant includes a nonionic surfactant.

In an additional example of the first, second, and third aspects and theabove examples, the suspension further includes a biocide.

In another example of the first, second, and third aspects and the aboveexamples, the suspension further includes a magnesium salt.

In a further example of the first, second, and third aspects and theabove examples, the suspension includes a potassium salt.

In an additional example of the first, second, and third aspects and theabove examples, the method further includes applying the filteredsolution to a reagent concentrate to form a reagent solution. Forexample, the reagent concentrate includes a nucleotide.

In another example of the first, second, and third aspects and the aboveexamples, the sensor is a pH sensor. In another example of the first,second, and third aspects and the above examples, the sensor is abiosensor.

In a further example of the first, second, and third aspects and theabove examples, the sensor is a semiconductor sequencing sensor.

In an additional example of the first, second, and third aspects and theabove examples, the method further includes repeating mixing andtitrating.

In another example of the first, second, and third aspects and the aboveexamples, the method further includes applying the dispersion to acartridge.

Note that not all of the activities described above in the generaldescription or the examples are required, that a portion of a specificactivity may not be required, and that one or more further activitiesmay be performed in addition to those described. Still further, theorder in which activities are listed are not necessarily the order inwhich they are performed.

In the foregoing specification, the concepts have been described withreference to specific embodiments. However, one of ordinary skill in theart appreciates that various modifications and changes can be madewithout departing from the scope of the invention as set forth in theclaims below. Accordingly, the specification and figures are to beregarded in an illustrative rather than a restrictive sense, and allsuch modifications are intended to be included within the scope ofinvention.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of features is notnecessarily limited only to those features but may include otherfeatures not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive-or and not to an exclusive-or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Also, the use of “a” or “an” are employed to describe elements andcomponents described herein. This is done merely for convenience and togive a general sense of the scope of the invention. This descriptionshould be read to include one or at least one and the singular alsoincludes the plural unless it is obvious that it is meant otherwise.

Benefits, other advantages, and solutions to problems have beendescribed above with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any feature(s) that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as a critical, required, or essentialfeature of any or all the claims.

After reading the specification, skilled artisans will appreciate thatcertain features are, for clarity, described herein in the context ofseparate embodiments, may also be provided in combination in a singleembodiment. Conversely, various features that are, for brevity,described in the context of a single embodiment, may also be providedseparately or in any subcombination. Further, references to valuesstated in ranges include each and every value within that range.

What is claimed is:
 1. A method of performing pH-sensitive processes,the method comprising: drawing a suspension from a reservoir, thesuspension including a surfactant and a solid buffer particulate andhaving a target pH, wherein the solid buffer particulate includes aceramic particulate, wherein the ceramic particulate is titanium dioxideor tin oxide; filtering the solid buffer particulate from the suspensionto form a filtered solution; and flowing the filtered solution over asensor.
 2. The method of claim 1, wherein the solid buffer particulatehas a point of zero charge of at least 1.2 pH units and not greater than10 pH units different than the target pH.
 3. The method of claim 2,wherein the point of zero charge is at least 2.0 pH units different thanthe target pH.
 4. The method of claim 1, wherein the target pH is in arange of 6 to
 8. 5. The method of claim 4, wherein the target pH is in arange of 6.8 to 8.0.
 6. The method of claim 1, wherein the ceramicparticulate is titanium dioxide or tin oxide.
 7. The method of claim 1,wherein the ceramic particulate is a fumed ceramic particulate.
 8. Themethod of claim 1, wherein the solid buffer particulate has a specificsurface area in the range of 50 m²/g to 350 m²/g.
 9. The method of claim1, wherein the solid buffer particulate has a specific surface area inthe range of 25 m²/g to 125 m²/g.
 10. The method of claim 1, wherein thesolid buffer particulate has a particle size in a range of 0.01 micronsto 1200 microns.
 11. The method of claim 10, wherein the particle sizeis in a range of 0.05 microns to 500 microns.
 12. The method of claim 1,wherein the surfactant includes a nonionic surfactant.
 13. The method ofclaim 1, wherein the suspension further includes a biocide.
 14. Themethod of claim 1, wherein the suspension further includes a magnesiumsalt or a potassium salt.
 15. The method of claim 1, further comprisingapplying the filtered solution to a reagent concentrate to form areagent solution.
 16. The method of claim 15, wherein the reagentconcentrate includes a nucleotide.
 17. The method of claim 1, whereinthe sensor is a biosensor.
 18. The method of claim 1, wherein the sensoris a semiconductor sequencing sensor.
 19. The method of claim 9, whereinthe specific surface area is in a range of 50 m²/g to 100 m²/g.
 20. Themethod of claim 11, wherein the particle size is in a range of 5.0microns to 100 microns.